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Kalil Abdullah

Kalil Abdullah

Program: Cancer Therapeutics

412-647-7614 abdullahkg@upmc.edu UPMC Cancer Pavilion
5150 Centre Ave
Pittsburgh PA
Summary

My laboratory is focused on developing novel clinical models of glioma and identifying druggable targets to facilitate early phase clinical trials.

Gliomas are intensely heterogenous tumors that not only contain numerous cell types, but also demonstrate the ability to transition between different phenotypic states. This complexity has made developing model systems that recapitulate human tumor biology both difficult and essential. Traditionally, models of gliomas are 2-dimensional cell lines and only represent certain subtypes of the highest-grade glioma, glioblastoma. This is because the unique biology of lower grade gliomas has prevented them from being studied either outside of the lab or in animals. We have created ex-vivo culture systems that allow us to investigate critical aspects of the tumor microenvironment, immune response, and discover targets for therapy. Our laboratory has previously shown the ability to establish lower grade glioma organoids in vitro, maintain those cultures for extended periods of time, hibernate, and then reanimate tumor tissue without loss of either genetic or phenotypic fidelity. Our work also includes extensive and sophisticated live-cell imaging analysis that allows for longitudinal, non-invasive assessment of organoid response to treatment.
Our organoid model systems, in addition to glioma stem cell and mouse models, allow us to perform highly sophisticated assessments of drug response across platforms, and identify rare but critical druggable targets in gliomas. These analyses include complex metabolic tracing and immune cell response assessment. Despite the fundamental principles of genomics, immunology, and cellular cancer biology that underlie our work, our group focuses on projects that have high potential for immediate clinical translation.

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Sameer Agnihotri

Sameer Agnihotri

Program: Cancer Biology

(412) 218-8456 sameer.agnihotri@pitt.edu Rangos Research Center, Room 7126
4401 Penn Avenue
Pittsburgh PA
Summary

The lab has a focus on several topics:
1) It is now appreciated that HGG glioma comprises of several molecular subgroups and that the genetics of pediatric and adult HGG are distinct. Therefore a “one size that fits all” approach to therapy will not be successful. The Agnihotri Laboratory interests include using next-generation sequencing technology to identify and validate driver alterations of various HGG with a focus on DIPG and non-histone mutated “RTK” Glioblastoma (GBM). 
2) A defining hallmark of glioblastoma and DIPG is altered tumor metabolism. The metabolic shift towards aerobic glycolysis with reprogramming of mitochondrial oxidative phosphorylation, regardless of oxygen availability, is a phenomenon known as the Warburg effect. In addition to the Warburg effect, glioblastoma tumor cells also utilize the tricarboxylic acid cycle/oxidative phosphorylation in a different capacity than normal tissue. The Agnihotri Laboratory investigates the metabolic dependencies of brain tumors and if they can provide therapeutic vulnerabilities.
3) The lab uses the genomic and metabolic information to build better representative brain tumor pre-clinical models for testing of novel therapies. Working closely with a clinical team use of these accurate models are essential to start early phase clinical trials.

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Katherine Aird

Katherine Aird

Program: Cancer Biology

katherine.aird@pitt.edu The Assembly
5051 Centre Ave
Pittsburgh PA
Summary

The Aird lab focuses on the reciprocal regulation between cellular metabolism and the cell cycle. The interplay between cell cycle and metabolism is bidirectional, although incompletely understood. While proliferating cells require energy and biomass, metabolites can also act as signaling molecules to impact epigenetic and transcriptional programs, thereby influencing biology beyond macromolecule needs. Our lab has made fundamental discoveries into how metabolism informs proliferative cell fate decisions by studying two extremes of proliferation: cancer and cellular senescence. Both cancer and senescent cells are highly metabolically active, yet the outcomes of this rewiring are distinct. We aim to ask fundamental questions related to how the cell cycle informs metabolic decisions and vice versa. Using cancer as a model system, we aim to answer fundamental questions on the bidirectional control of metabolism and the cell cycle.

Our specific questions:

1)    How do metabolic cues lead to differential cell cycle decisions? 

2)    How does cell cycle derangement affect metabolism and what are the consequences of this on intrinsic and extrinsic signaling?

3)    What are the consequences of bidirectional cell cycle and metabolism programs on intrinsic and extrinsic signaling? 

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Oleg Akilov

Oleg Akilov

Program: Cancer Immunology and Immunotherapy

412-647-4200 akilovoe@upmc.edu 3601 Fifth Avenue, 5th Floor
Pittsburgh PA
Summary

Oleg E. Akilov, MD, PhD, is an Assistant Professor of the Department of Dermatology at the University of Pittsburgh and a Director of the Cutaneous Lymphoma Program and Extracorporeal Photopheresis Unit. Dr. Akilov directs Cutaneous Lymphoma Program providing the full spectrum of management of all stages of cutaneous lymphoma. He serves as a principal investigator on multiple clinical trials in cutaneous lymphoma. Additionally, Dr. Akilov is very enthusiastic about resident education and mentoring future dermatologists.

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Jonathan Alder

Jonathan Alder

Program: Genome Stability

412-624-8681 alderju@upmc.edu BST W1246
200 Lothrop St.
Pittsburgh PA
Summary

My research focuses on understanding the role of telomere length in human health and disease. Telomeres are caps on the ends of each of chromosomes and shorten as we age. All cancer cells must find a way to maintain their telomeres to sustain tumor growth. Our lab investigates mechanisms that tumors use to maintain their telomeres to identify potential targets for therapeutic intervention. We hope these studies will lead to a deeper understanding of how telomere maintenance contributes to cancer pathogenesis and potentially inform rational therapies.

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Daniel Altschuler

Daniel Altschuler

Program: Cancer Therapeutics

412-648-9751 altschul@pitt.edu Biomedical Science Tower, E-1348
200 Lothrop Street
Pittsburgh PA
Summary

Dr. Altschuler's laboratory studies mechanisms of signal transduction by the second messenger cAMP in cell proliferation. cAMP-dependent protein kinase (PKA) and Exchange protein activated by cAMP (Epac) represent the main effectors of cAMP action. Both pathways converge at the level of the small GTPase Rap1b, via its Epac-mediated activation and PKA-mediated phosphorylation. The role of Rap1 activation (Epac) and phosphorylation (PKA) coordinating the early rate-limiting events in cAMP-dependent cell proliferation are studied using a multidisciplinary approach including molecular and cellular biology techniques in vitro, as well as in vivo validation using transgenic/knock in technologies in endocrine tumor models.

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Zandrea Ambrose

Zandrea Ambrose

Program: Cancer Virology

(412) 624-0512 zaa4@pitt.edu 450 Technology Drive
520 Bridgeside Point 2
Pittsburgh PA
Summary

Millions of people are infected with both HIV and HBV. Morbidity and mortality in HIV/HBV co-infection is higher than mono-infections and co-infection accelerates HBV-related liver disease with more frequent development of hepatocellular carcinoma (HCC), particularly when CD4 cell counts are low. Together with Dr. Haitao Guo, we are developing a murine model to study pathogenesis and HCC progression during HIV/HBV co-infection, which will be essential in evaluating mechanisms of infection as well as novel prevention methods, improved therapies, and curative strategies.

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Leonard Appleman

Leonard Appleman

Program: Cancer Therapeutics

412-648-6507 applemanlj@upmc.edu UPMC Cancer Pavilion
5230 Center Ave., Suite 567
Pittsburgh PA
Research Interests and Keywords
  • experimental cancer therapeutics
  • Kidney cancer and other genitourinary malignancies
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Dooman Arefan

Dooman Arefan

Program: Cancer Epidemiology and Prevention

doa14@pitt.edu 3240 Craft Pl
Room 327
Pittsburgh PA
Summary

As a Research Assistant Professor at the University of Pittsburgh, Department of Radiology, I am currently conducting cancer-related research that utilizes my extensive training in image processing and machine learning for clinical/translational studies. My expertise in both medical imaging and computational science allows me to identify unmet needs in medical imaging and employ cutting-edge computational techniques to address challenges in the field. I have previously worked on several research projects utilizing machine learning techniques for breast cancer diagnosis, prognosis, and risk assessment. I am seeking membership at UPMC Hillman Cancer Center to collaborate with researchers in the field and contribute to the advancement of cancer research. I envision my role as a researcher who will utilize my expertise in medical imaging and machine learning to develop innovative solutions for cancer diagnosis, prognosis, and treatment. I am also keen on sharing my knowledge and skills with the research community and contributing to the training of the next generation of researchers in the field of cancer imaging and machine learning

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Karen Arndt

Karen Arndt

Program: Genome Stability

412-624-6963 arndt@pitt.edu A316 Langley Hall
4249 Fifth Ave
Pittsburgh PA
Summary

A fundamental question in molecular biology is how organisms interpret the vast amounts of information encoded in their genomes. The Arndt lab uses a wide range of experimental approaches to study the first step in gene expression, the synthesis of mRNA by RNA polymerase II, with a focus on the mechanisms that regulate transcription in the chromatin environment of a eukaryotic cell.  Specific areas of interest include the mechanisms that couple histone modifications to active transcription, the coordination among different epigenetic modifications and their impact on transcription elongation and termination, and the molecular functions of core RNA polymerase II elongation factors with broad and conserved effects on the eukaryotic transcriptome.  The fundamental importance of understanding eukaryotic transcriptional regulation is evident from the large number of human developmental defects and diseases, including cancer and AIDS, that arise when cellular transcription factors are altered by mutation or commandeered by viral proteins.

Research Interests and Keywords
  • cellular transcription
  • Chromatin
  • Gene Expression
  • mRNA synthesis
  • RNA polymerase II
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Maninjay Atianand

Maninjay Atianand

Program: Cancer Immunology and Immunotherapy

412-383-0472 atianand@pitt.edu 200 Lothrop St
W1046 BST
Pittsburgh PA
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